Tags

Type your tag names separated by a space and hit enter

Oxidative stress and inflammation in Parkinson's disease: is there a causal link?
Exp Neurol 2005; 193(2):279-90EN

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the many pathogenic mechanisms thought to contribute to the demise of these cells, dopamine-dependent oxidative stress has classically taken center stage due to extensive experimental evidence showing that dopamine-derived reactive oxygen species and oxidized dopamine metabolites are toxic to nigral neurons. In recent years, however, the involvement of neuro-inflammatory processes in nigral degeneration has gained increasing attention. Not only have activated microglia and increased levels of inflammatory mediators been detected in the striatum of deceased PD patients, but a large body of animal studies points to a contributory role of inflammation in dopaminergic cell loss. Recently, postmortem examination of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia decades after drug exposure, suggesting that even a brief pathogenic insult can induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD. In the past few years, various pathways have come to light that could link dopamine-dependent oxidative stress and microglial activation, finally ascribing a pathogenic trigger to the chronic inflammatory response characteristic of PD.

Authors+Show Affiliations

Department of Pharmacology, Danish University of Pharmaceutical Sciences, Jagtvej 160, 2200 Copenhagen, Denmark.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

15869932

Citation

Hald, Andreas, and Julie Lotharius. "Oxidative Stress and Inflammation in Parkinson's Disease: Is There a Causal Link?" Experimental Neurology, vol. 193, no. 2, 2005, pp. 279-90.
Hald A, Lotharius J. Oxidative stress and inflammation in Parkinson's disease: is there a causal link? Exp Neurol. 2005;193(2):279-90.
Hald, A., & Lotharius, J. (2005). Oxidative stress and inflammation in Parkinson's disease: is there a causal link? Experimental Neurology, 193(2), pp. 279-90.
Hald A, Lotharius J. Oxidative Stress and Inflammation in Parkinson's Disease: Is There a Causal Link. Exp Neurol. 2005;193(2):279-90. PubMed PMID: 15869932.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress and inflammation in Parkinson's disease: is there a causal link? AU - Hald,Andreas, AU - Lotharius,Julie, PY - 2004/09/29/received PY - 2005/01/13/revised PY - 2005/01/19/accepted PY - 2005/5/5/pubmed PY - 2005/7/16/medline PY - 2005/5/5/entrez SP - 279 EP - 90 JF - Experimental neurology JO - Exp. Neurol. VL - 193 IS - 2 N2 - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the many pathogenic mechanisms thought to contribute to the demise of these cells, dopamine-dependent oxidative stress has classically taken center stage due to extensive experimental evidence showing that dopamine-derived reactive oxygen species and oxidized dopamine metabolites are toxic to nigral neurons. In recent years, however, the involvement of neuro-inflammatory processes in nigral degeneration has gained increasing attention. Not only have activated microglia and increased levels of inflammatory mediators been detected in the striatum of deceased PD patients, but a large body of animal studies points to a contributory role of inflammation in dopaminergic cell loss. Recently, postmortem examination of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia decades after drug exposure, suggesting that even a brief pathogenic insult can induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD. In the past few years, various pathways have come to light that could link dopamine-dependent oxidative stress and microglial activation, finally ascribing a pathogenic trigger to the chronic inflammatory response characteristic of PD. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15869932/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(05)00036-1 DB - PRIME DP - Unbound Medicine ER -